JP2020513577A - SECURITY DIAGNOSTIC TEST ASSAYS AND RELATED DEVICES AND METHODS OF USE THERE - Google Patents

Abstract

Disclosed herein is a secure assay device, which is: an assay or test device that provides at least one result that is optical in response to at least one particle of interest, at least one marker, or a combination thereof. At least one surface exhibiting changes; at least one multilayer coating that at least partially covers the assay membrane, assay device, or combination thereof; user visualization of the optical change, at least one result, or combination thereof. An assay or test device with a multilayer coating that blocks or diminishes. Disclosed herein are secure readers and methods of utilizing secure assay devices and secure readers.

Description

  This Patent Cooperation Treaty application claims priority to US Provisional Application No. 62432022 filed December 9, 2016, US Patent Application No. 15430698 filed February 13, 2017. Both applications are jointly owned, the disclosures of which are incorporated herein by reference in their entireties.

  The field of the present subject matter is diagnostic test assays, layered materials and coating materials that at least partially function to optically encode the results of diagnostic test assays and related devices.

  There are several methods for testing health and disease, but in general, tests or assays can be categorized as those performed by physicians and health care workers, and those performed by patients. In the latter case, such as in the case of pregnancy tests, the test results are immediately read by the patient and are open for interpretation. While self-examination and self-assessment of results are convenient for the patient, they may not be the best method from a patient welfare or public policy perspective. This is especially true for infectious diseases such as HIV and other STDs (sexually transmitted diseases), as well as major health conditions including cancer and pregnancy.

  Others such as food testing, crop testing, veterinary applications, substance abuse testing, biodefense applications using IVD (in vitro diagnostics) technology and immunoassays (such as lateral flow tests, flow-through tests, rapid diagnostic tests, microarray formats) For types of tests, it may be advantageous to have the results reviewed and interpreted by a third party company or individual due to confidentiality issues, misinterpretation issues, or issues arising from the test subject hiding or misreporting the results. obtain. In such cases, the test results may be first tested by a third party individual (eg, a medical or laboratory professional) and / or a machine (eg, reader) to avoid misunderstanding or misinterpretation of the test results. It is necessary and / or preferred to be analyzed and interpreted.

  There are currently various types of assays with optical output on the market, including chromatography, fluorescence, up-converting phosphors and luminescence. Chromatographic assays, and labels typically developed using gold, silver, carbon, latex and other visible particles display test results in the form of changes in color, contrast and / or visual intensity. By its very nature, the results of these tests are visible to the user or operator, and there is currently no method available to partially hide the test results from the user or unauthorized operator.

  At the same time, there are several ways to indirectly address this issue of test result confidentiality and security, but with significant drawbacks. In one type of assay, the user activates the assay using his / her sample (eg, blood, bodily fluid, etc.) and then activates the activated test before the test results become visible. Need to be returned to a medical facility (laboratory, hospital, clinic, etc.) or other facility. Once the test results are received, they are read either visually or using the facility's digital equipment. Written communication is then followed by results returned to the patient or authorized user, or some other action, such as a follow-up visit to a healthcare provider.

  There are some drawbacks to these types of tests. First, the time between test activation or sample collection by the end user (ie patient) and its receipt and analysis by the facility is typically quite long (ie up to a few days). Immunoassay tests are not stable for long periods and reactions do not stop for hours or even days. Therefore, these types of tests (eg, lateral flow assays) are typically to be interpreted in less than 15 minutes, otherwise these tests are ineffective, inaccurate and ineffective. Becomes Furthermore, environmental conditions are not precisely controlled during the transport of activated test / assays, potentially affecting assay / test results.

  Another indirect method is to configure the assay with a number of different features or patterns that become visible to the user as the test evolves. However, the meaning of such visible features is hidden from the user. Interpreting these requires the reader using the algorithm to derive the test result; the test result remains hidden within the reader and is secretly communicated to the facility. Although this method works extremely well, the need to incorporate more than one test feature per analyte in the assay is a major disadvantage, requires more expensive development, and usually leads to compromises in test performance. ..

  Alternatively, for security purposes (and also for better sensitivity), fluorescence and upconverting phosphor assay techniques are used. The test results are invisible to the naked eye and can only be read by a special reader using a special light source (eg UV light). However, these fluorescence-based techniques can only offer limited testing applications, and fluorescent labels are significantly more expensive than visible markers (such as commonly used gold nanoparticles). In addition, significant upfront investment in R & D and equipment is required.

  Luminescent assays are generally too weak to be read visually and produce optical results that require a sensitive reader. These assays meet confidentiality requirements; by their very nature, they are only available in limited niche applications.

  Rapid diagnostic assays or tests (RDTs) play an important and growing role in a spectrum of treatments worldwide. Administered either at points of care in clinics, hospitals, urban and remote clinics, or by paramedics, providing immediate results, these tests offer improved access, lower cost, and better Contributing to quality medical care. An increasing number of RDTs are available for home use by patients and the general public for testing acute and chronic conditions. The major technique used for RDT is lateral flow immunochromatographic analysis (LFI), followed by lateral flow immunofluorescence analysis. Global annual LFI test and service value is $ 18 billion according to BCC Research. RDT is also available in other variants of immunoassays, such as flow-through and dipstick tests, and in other chemical or biochemical methods. Indeed, the contemplated embodiments described herein are applicable to any RDT using changes in optical properties as the mechanism of operation. All RDTs typically include an active moiety that interacts with the analyte in the sample, and the surrounding structure; together form an assay device suitable for treatment by the patient or user.

  To this end, and to achieve confidentiality and security objectives, it makes it difficult for end-users or operators to visually interpret the test results, but a dedicated reading device ensures that the results are passed to the laboratory or government. It would be desirable to create and utilize an assay device that requires secure communication to an organization. Also, it is desirable to ensure that any solution is cost-effective and reliable; it is applicable to most existing assay technologies with minimal adaptation.

  Disclosed herein is a secure assay device, which is: an assay or test device that provides at least one result that is optical in response to at least one particle of interest, at least one marker, or a combination thereof. At least one surface exhibiting a change; at least one multi-layer coating at least partially covering the assay membrane, assay device or combination thereof, wherein the user visualization of the optical change, at least one result, or a combination thereof. Assay or test device with a multilayer coating that blocks or reduces

  A secure reader is: a set of control electronics, a digital camera component, a lighting component, a housing component, an assay or test device that provides at least one result, at least one particle of interest, at least one particle. An assay or test device comprising at least one surface exhibiting an optical change in response to a marker, or a combination thereof, and at least one multilayer coating at least partially covering the assay membrane, the assay device, or a combination thereof. And blocking or reducing user visualization of the optical change, at least one result, or a combination thereof.

  A method for providing a confidential in vitro diagnostic test is: providing an assay or test device that provides at least one result, wherein the assay or test device comprises at least one particle of interest, at least one marker, or a combination thereof. Providing at least one surface that exhibits an optical change in response to: providing at least one multilayer coating that at least partially covers the assay membrane, assay device, or combination thereof; Blocking or reducing user visualization of optical changes, at least one result, or a combination thereof; utilizing a reader to obtain test results invisible to the user, and others Provide results securely and confidentially to That and a step.

3 illustrates a coating scheme for contemplated embodiments. 3 illustrates an assay device format of contemplated embodiments. 1 illustrates a reader system of contemplated embodiments. 1 illustrates an embodiment of a reader system. Shows the contemplated method. Figure 3 shows a secure assay compared to a conventional assay or test. 2 illustrates another contemplated method.

  Assay devices, which can also be in vitro diagnostic assay devices and reporting instruments, have been developed and described herein, including rapid diagnostic devices, assay membranes, and test results for third party physicians, healthcare providers or reviews. It has a coating material that allows it to be reviewed securely and accurately by an ar. In some embodiments, contemplated test results can additionally be encrypted, thereby protecting patients and the general public until the results can be reviewed and interpreted. The solution disclosed herein is not only cost effective but reliable. Finally, in some instances, the results can be communicated to a laboratory or an administrative body, or can be communicated automatically, if that option is desired for records management or documentation.

  Unlike existing techniques and protocols, contemplated embodiments can be readily applied to any assay that is commercially available or in development. Assay manufacturers and developers can improve the technology with contemplated embodiments. Plastic layers are already widely used in the art to prevent contamination and these layers can be replaced with the intended coatings or layers, or multilayer coating layers. Thus, the cost of the contemplated embodiment per test is very low, if not zero, for assay manufacturers, those who use the assay, and those who integrate the assay into the reader design.

  In particular, a secure assay device is disclosed herein, which is: an assay or test device that provides at least one result in response to at least one particle of interest, at least one marker, or a combination thereof. At least one surface exhibiting an optical change and at least one multilayer coating at least partially covering the assay membrane, assay device, or combination thereof, wherein the optical change, the at least one result, or a combination thereof. An assay or test device with a multi-layer coating that blocks or reduces user visualization.

  As used herein, the expression "optical change" means there is a physical change, an optical change, or a combination thereof, to analyze an observer, user, or result. The device used detects changes in the surface or properties of the surface.

  In contemplated embodiments, at least one particle of interest, at least one marker, or combination thereof comprises an analyte, antibody, molecule, virus, bacterium, cell, or combination thereof.

  A secure reader is: a set of control electronics, a digital camera component, a lighting component, a housing component, an assay or test device that provides at least one result, at least one particle of interest, at least one particle. An assay or test device comprising at least one surface that exhibits an optical change in response to a marker, or a combination thereof; and at least one multi-layer coating at least partially covering the assay membrane, assay device, or combination thereof. A multilayer coating that blocks or reduces user visualization of optical changes, at least one result, or a combination thereof.

  A method of performing a confidential in vitro diagnostic test is: providing an assay or test device that provides at least one result, wherein the assay or test device is attached to at least one particle of interest, at least one marker, or a combination thereof. Providing at least one surface responsive to exhibiting an optical change; providing at least one multilayer coating that at least partially covers the assay membrane, assay device, or combination thereof, wherein the multilayer coating comprises Blocking or reducing user visualization of optical changes, at least one result, or a combination thereof; utilizing a reader to obtain test results invisible to the user, and others Providing results securely and confidentially And a step.

  In contemplated embodiments, novel optical techniques have been developed for safe, secure, and accurate diagnostics using in vitro diagnostic techniques. We also designed a digital readout system to analyze and interpret the immunoassay, encrypt the test results, and automatically share them with a third party.

  Immediately after test activation (typically 5 to 20 minutes), but at the same time end to provide a safe, sensitive, and accurate diagnosis using in vitro diagnostic or IVD techniques. The readout or review may be completed or should be communicated after a predefined time interval that does not provide results to the user. An integrated reading device (eg, a special reading device) can encrypt test results and automatically share them in medical facilities (laboratory, hospital, clinic, etc.).

  In particular, an in vitro diagnostic test and assay device 200 has been developed and shown in FIGS. 1 and 2, which comprises an assay membrane 260 and a multi-layer coating 140 that at least partially covers the assay membrane 260 and one or more multi-layer coatings. 140 blocks user visualization of tests, results, or combinations thereof (not shown), such as on the read side 230. In some optional embodiments, assay membrane 260 can be enclosed within outer shell 250. The multi-layer coating 140 can be placed directly on the assay membrane 260, either as a coating or as a separate layer, either on the assay membrane or on the outer shell 250, and optionally on the membrane 260 or the bottom of the shell 250. it can. A contemplated secure assay device that provides confidentiality and security of test results may be referred to by the trade name SECASSAY ™. In contemplated embodiments, the assay device may be a fluorescent assay, a microfluidic assay, or a combination thereof.

  A secure reader 300 is also disclosed and illustrated in FIGS. 3 and 4, which includes: a set of control electronics 320, a digital camera component 330, a lighting component 350, 360, a housing component 310, a quick diagnostic test tray ( 3) (not shown in FIG. 3) with a tray capable of holding at least one rapid diagnostic test such as SECASSAY ™ or a secure assay device 100, the reader being capable of performing two or more different rapid diagnostic tests. Can respond.

  The contemplated secure assay device 100 shown in FIGS. 1 and 2 includes an assay or test 110 positioned in a test tray (not shown), and a multi-layer coating 140 that at least partially covers the assay 110. , Multi-layer coatings block user visualization of tests, results, or combinations thereof. The digital camera element, shown as 330 in FIG. 3, along with associated camera lenses, filters, or combinations 340, and control electronics 320 can be used in mobile phones, smartphones, digital cameras, other rapid test readers, or other It may be part of a similar device. In contemplated embodiments, the multi-layer coating 140 may be partially reflective, partially transparent, or a combination thereof. In some contemplated embodiments, the multi-layer coating 140 can further comprise one or more layers that are sensitive to light polarization, wavelength, intensity, or combinations thereof.

  The contemplated handheld rapid diagnostic reader is any suitable, including those disclosed in corresponding US patent application Ser. No. 14 / 313,615, which is co-owned and incorporated herein by reference in its entirety. Any reading device may be used. An important consideration regarding the suitability of a reader is the ability to read a secure assay device 100, as described in the previous paragraph.

  In contemplated embodiments, as previously described, the secure assay device is designed so that its bottom side is located on or near the transfer element. The upper side is designed so that the active part of the membrane containing the test indication is in the field of view of the reader element. As disclosed herein, the assay membrane is either wholly or partially covered with at least one multi-layer coating having adjustable transmission. On the bottom side of the coated assay membrane is a transfer element such as a light emitting diode or LED. The transmissive element transmits light to and through the optional outer shell and through the coated assay membrane.

  In some embodiments, contemplated assay membranes include a side facing the transfer element and another side having an active region of interest. The side facing the transfer element is the side of the assay membrane that first contacts the light or energy from the transfer element. In these embodiments, the active area side of interest is the side of the coated assay membrane that faces the digital camera element (detector) in the reader for receiving and reviewing the results.

  In other embodiments, contemplated assay membranes comprise active and inactive sides, which may be adjacent to each other on the same surface side of the contemplated assay membrane. The active side of these contemplated assay membranes is the side facing the detector that interacts with the reflective or fluorescent element and at the same time receives the result. In these embodiments, the reflective or fluorescent element can provide the light or energy that is produced by the coated assay analysis membrane from one angle or for a period of time, after which the detector or reader is switched to another angle. Review the results from or when the reflective or fluorescent elements are no longer active. In these embodiments, the first side may include or be coupled to a reflective or fluorescent element and a reader or detector, and the second side may only be joined to the inner cavity.

  Contemplated visual encryption methods, embodiments and devices can be used to assay whole assay membranes or test packages (eg, lateral flow assays, vertical flow immunoassays, flow-through assays, or other IVD tests) as shown in FIG. Depending on a multi-layer coating with adjustable transmission used to cover all (all four sides) or partially (one or more sides). 1 shows a test or assay 110 with an optional bandpass filter and polarizing layer 120 on each side, it being understood that they may be on one side or not at all. I want to be done. In addition, there are partially reflective / partially transparent coatings 130 on each side, but it should be understood that they can only be on one side. Contemplated reflective or transparent coatings can comprise at least one layer, and in some cases two or more layers. These contemplated reflective or transparent coating layers themselves can be multilayer coatings. These coatings or layered materials are similar to unidirectional or bidirectional mirrors.

  In some embodiments, optional polarizers and / or “wavelength” bandpass filters or layers 120 can be used as or in combination with coating layers, which have a greater range. Can be optimized on a per assay basis to block user visualization of tests and results.

  The partially reflective, partially transparent, or a combination thereof layer can be any material as long as the following principles are met. One side of the material is illuminated, or energy is applied to that side, and the other side is relatively dark, or in the absence of apparent light or energy present in space, from the dark or low energy side to the individual Can be observed, or from the detector, but not vice versa.

  The optical properties (reflectance and transmittance) determine the material thickness or the individual layers of material, or the composition or concentration of the coating material, depending on the test type, device type, reader or detector type, or a combination thereof. It can be adjusted by changing. These materials can be covered with metal (eg, silver or gold) and can be used extensively in interrogation rooms, security surveillance decks or security cameras and the like.

  In other embodiments, the additional use of polarizers and bandpass filter layers can add an extra level of confidentiality, security, or a combination thereof. Because end users may attempt to read the test in strong ambient light, sunlight, or other commercially available light sources, the assay may require special polarization sensitive filters, bandpass (narrow or wide) filters, or those filters. It can be coated in combination, or additionally, so that only light with a particular polarization and wavelength, or energy, can pass the test.

  A contemplated reader 300, such as the previously disclosed conventional reader, has three illumination and readout modes: fluorescence 360, reflection 360 and transmission 350, as shown in FIGS. 3 and 4. It works on the basis of recording images in one or more of the lighting modes or schemes. The reflective mode is used in most commercially available readers as it clearly supports visual readout, is easy to implement and provides comparable results. Each illumination scheme can be customized for illumination angles, different polarizations, wavelengths, transmission efficiencies and light intensities for reading visually encoded assays. The readout system thus optimized is equivalent to a decoder. The camera system 330 records an image of the secure assay 100 that becomes digitally visible and can process the image to quantify the signal and generate test results. In FIG. 4, the contemplated secure assay 200 is placed on top of the transmit LED 350, shown as reference numeral 370.

  A contemplated lighting component that illuminates a contemplated secure assay device can be from the opposite side of the device, from a digital camera component, or depending on the needs and design of the reader, assay, or combination thereof. Illuminate the device from the same side as the digital camera component. In embodiments where the illumination component illuminates the assay device from the same side as the digital camera component, it does so to excite fluorophores and upconverting phosphors in fluorescence and upconverting phosphor-based assays. The contemplated reader comprises a lighting component that illuminates the secure assay device with a wavelength compatible with the multilayer coating in the secure assay device.

  The contemplated method can also be applied to fluorescent assays, as the contemplated readers and reader solutions utilize off-axis illumination schemes and are reflected by the coating (s). This is because the light does not reach the camera, while the membrane can be excited by the partially transmitted excitation light and emit a fluorescent signal that can be recorded by the reader system. An embodiment of the contemplated readout system 300 is shown in FIG.

  As shown in FIG. 5, the contemplated method begins with conventional test / assay / device 110, step 510, and conventional test using at least one multi-layer coating 140 to create a secure assay 200. 520 / at least partially covering the assay / device 110, inserting 530 the secure assay 200 into the reader system 300, and using 540 the reader system 300 to analyze the secure assay 200. , Sending the test / assay / device results to an authorized person or location (not shown). FIG. 6 shows a conventional assay in which the test results are visible to the observer 610 and the assay of the contemplated embodiment in which the test results are hidden to the observer 620.

  As shown in FIG. 7 and as discussed above, a method 700 of providing a confidential in vitro diagnostic test includes: providing 710 an assay or test device that provides at least one result, the assay or test device. Comprising at least one surface exhibiting an optical change in response to at least one particle of interest, at least one marker or a combination thereof; at least partially covering the assay membrane, assay device, or combination thereof. Providing 720 at least one multi-layer coating, wherein the multi-layer coating blocks or reduces user visualization of the optical change, at least one result, or a combination thereof; And other things to get Results secure and a step 730 utilizing the reading device in order to provide secretly.

  As disclosed and discussed above, contemplated embodiments can be readily applied to any assay that is commercially available or in development. Assay manufacturers and developers can improve the technology with contemplated embodiments. Plastic layers are already widely used in the art to prevent contamination and these layers can be replaced with the intended coating or multilayer coating layers. Thus, the cost of the contemplated embodiments per test, if not zero, is extremely low for assay manufacturers, those who use the assay, and those who incorporate the assay into the reader design.

  Thus, particular embodiments, methods of layered and coating materials for diagnostic test devices are disclosed. However, it will be apparent to those skilled in the art that many further modifications are possible other than those already described without departing from the inventive concept herein. Therefore, the subject matter of the invention is not limited except for the purpose of the disclosure herein. Moreover, in interpreting the specification and claims, all terms should be construed in the broadest possible manner consistent with the subject matter. In particular, the terms "comprising" and "comprising" are to be construed as referring to the element, component or step in a non-exclusive manner, and the referenced element, component or step is explicitly It shall indicate that it may be present in, utilized in, or combined with other elements, components, or steps that are not referenced.

Claims (15)

A secure assay device,
Assay or test device providing at least one result, comprising at least one surface exhibiting an optical change in response to at least one particle of interest, at least one marker, or a combination thereof. When,
At least one multilayer coating that at least partially covers the assay membrane, assay device, or combination thereof, blocking or reducing user visualization of optical changes, at least one result, or combination thereof. With coating,
Secure assay device.   The secure assay device of claim 1, wherein the at least one particle of interest, the at least one marker, or a combination thereof comprises an analyte, antibody, molecule, virus, bacterium, cell, or combination thereof.   The secure assay device of claim 1, wherein the assay device is a lateral flow and / or vertical flow immunoassay.   The secure assay device of claim 1, wherein the assay device is a fluorescent assay.   The secure assay device of claim 1, wherein the assay device is a microfluidic device.   The secure assay device of claim 1, wherein the multi-layer coating comprises adjustable transmission.   The secure assay device of claim 1, wherein the multilayer coating is partially reflective.   The secure assay device of claim 1, wherein the multilayer coating is partially transparent.   The secure assay device of claim 1, wherein the multilayer coating further comprises one or more layers sensitive to light polarization, wavelength, or intensity. A secure reader,
A set of control electronics,
Digital camera components,
Lighting components,
Housing components,
Assay or test device providing at least one result, comprising at least one surface exhibiting an optical change in response to at least one particle of interest, at least one marker, or a combination thereof. When,
At least one multilayer coating that at least partially covers the assay membrane, assay device, or combination thereof, blocking or reducing user visualization of optical changes, at least one result, or combination thereof. Secure reader with coating.   11. The secure reader of claim 10, comprising an illumination component that illuminates the secure assay device from the side opposite the digital camera component.   11. The secure reader of claim 10, comprising an illumination component that illuminates the secure assay device from the same side as the digital camera component.   11. The secure reader of claim 10, comprising an illumination component that illuminates the secure assay device with a wavelength compatible with the multi-layer coating in the secure assay device.   11. The illumination component illuminating a secure assay device from the same side as the digital camera component to excite fluorophores and upconverting phosphors in fluorescence and upconverting phosphor-based assays. The secure reader described. A method of performing a confidential in vitro diagnostic test, comprising:
Providing an assay or test device that provides at least one result, wherein the assay or test device exhibits an optical change in response to at least one particle of interest, at least one marker, or a combination thereof. A step comprising one surface;
Providing at least one multi-layer coating at least partially over an assay membrane, assay device, or combination thereof, wherein the multi-layer coating is a user visualization of an optical change, at least one result, or a combination thereof. Block or reduce the steps,
Utilizing a reader to obtain test results that are invisible to the user, and to securely and confidentially provide results to others.
Method.

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